title: Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa.
abstract: A recessive mutation in the tub gene causes obesity, deafness and retinal degeneration in tubby mice. The tub gene is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates and invertebrates. The TULP proteins share a conserved carboxy-terminal region of approximately 200 amino-acid residues. Here we report the analysis of the human gene TULP1, which is expressed specifically in the retina. Upon analysing 162 patients with nonsyndromic recessive retinitis pigmentosa (RP) and 374 simplex cases of RP, we found two who were compound heterozygotes for mutations that cosegregated with disease in the respective families. Three of the mutations are missense changes affecting the conserved C-terminal region; the fourth mutation affects a splice donor site upstream of this region. Our data suggest that mutations in TULP1 are a rare cause of recessive RP and indicate that TULP1 has an essential role in the physiology of photoreceptors.
authors.affiliation: Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Hagstrom
authors.forename: M A
authors.initials: MA
authors.lastname: North
authors.forename: P L
authors.initials: PL
authors.lastname: Nishina
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D051379:Mice; D009679:Nuclear Family; D010375:Pedigree; D017354:Point Mutation; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C105443:TULP1 protein, human; C491353:Tulp1 protein, mouse